ERM transactivation is up-regulated by the repression of DNA binding after the PKA phosphorylation of a consensus site at the edge of the ETS domain

The final step of the transduction pathway is the activation of gene transcription, which is driven by kinase cascades leading to changes in the activity of many transcription factors. Among these latter, PEA3/E1AF, ER81/ETV1, and ERM, members of the well conserved PEA3 group from the Ets family are involved in these processes. We show here that protein kinase A (PKA) increases the transcriptional activity of human ERM and human ETV1, through a Ser residue situated at the edge of the ETS DNA-binding domain. PKA phosphorylation does not directly affect the ERM transactivation domains but does affect DNA binding activity. Unphosphorylated wild-type ERM bound DNA avidly, whereas after PKA phosphorylation it did so very weakly. Interestingly, S367A mutation significantly reduced the ERM-mediated transcription in the presence of the kinase, and the DNA binding of this mutant, although similar to that of unphosphorylated wild-type protein, was insensitive to PKA treatment. Mutations, which may mimic a phosphorylated serine, converted ERM from an efficient DNA-binding protein to a poor DNA binding one, with inefficiency of PKA phosphorylation. The present data clearly demonstrate a close correlation between the capacity of PKA to increase the transactivation of ERM and the drastic down-regulation of the binding of the ETS domain to the targeted DNA. What we thus demonstrate here is a relatively rare transcription activation mechanism through a decrease in DNA binding, probably by the shift of a non-active form of an Ets protein to a PKA-phosphorylated active one, which should be in a conformation permitting a transactivation domain to be active.

Définition en discours de l'idéal-type eurorégional. Consensus et zones d'ombre autour d'une politique expérimentale

L'article examine comment s'affirme l'idéal-type émergent des eurorégions en Europe. En analysant les discours produits par des institutions, des acteurs économiques et des médias, nous reconstituons la définition du projet eurorégional à partir des diverses positions énonciatives et indépendamment des langues ou de la localisation géographique des eurorégions. D'un côté, les résultats mettent en évidence des métaphores caractéristiques du discours politique européen (la construction, l'expérimentation, le corps) qui contribuent à instaurer l'imaginaire d'un continuum territorial en Europe. D'un autre côté, les résultats dévoilent des zones d'ombre (dissensions, approximations, dispersions, concurrence) qui rendent la définition du projet eurorégional floue et difficile à appréhender pour le citoyen. L'analyse s'appuie sur un corpus authentique et multilingue en vue de déceler des régularités relatives au discours eurorégional. Elle mobilise des résultats textométriques simples mais vérifiables qui servent de repères à l'analyse qualitative.